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tRNAs are codon decoders that convert the transcriptome into the proteome. The field of tRNA research is excited by the increasing discovery of specific tRNA modifications that are installed at specific, evolutionarily conserved positions by a set of specialized tRNA-modifying enzymes and the biogenesis of tRNA-derived regulatory fragments (tsRNAs) which exhibit copious activities through multiple mechanisms. Dysregulation of tRNA modification usually has pathological consequences, a phenomenon referred to as "tRNA modopathy". Current evidence suggests that certain tRNA-modifying enzymes and tsRNAs may serve as promising diagnostic biomarkers and therapeutic targets, particularly for chemoresistant cancers. In this review, we discuss the latest discoveries that elucidate the molecular mechanisms underlying the functions of clinically relevant tRNA modifications and tsRNAs, with a focus on malignancies. We also discuss the therapeutic potential of tRNA/tsRNA-based therapies, aiming to provide insights for the development of innovative therapeutic strategies. Further efforts to unravel the complexities inherent in tRNA biology hold the promise of yielding better biomarkers for the diagnosis and prognosis of diseases, thereby advancing the development of precision medicine for health improvement.

Asunto(s)

Neoplasias , ARN de Transferencia , Humanos , ARN de Transferencia/metabolismo , ARN de Transferencia/genética , Neoplasias/genética , Neoplasias/metabolismo , Procesamiento Postranscripcional del ARN/genética , ARN Pequeño no Traducido/genética , ARN Pequeño no Traducido/metabolismo , Animales

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BACKGROUND: Mesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms. METHODS: This prospective, self-controlled clinical study was conducted at Henan Provincial People's Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation. RESULTS: Forty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1ß, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy. CONCLUSION: UMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines. TRIAL REGISTRATION: The study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.

Asunto(s)

Colitis Ulcerosa , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Cordón Umbilical , Humanos , Colitis Ulcerosa/terapia , Colitis Ulcerosa/patología , Femenino , Masculino , Adulto , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Trasplante de Células Madre Mesenquimatosas/métodos , Cordón Umbilical/citología , Persona de Mediana Edad , Estudios Prospectivos , Citocinas/metabolismo , Citocinas/sangre , Resultado del Tratamiento

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Severe fever with thrombocytopenia syndrome (SFTS) is a recently identified infectious ailment triggered by a new strain of bunyavirus. It is distinguished by elevated fatality rates, ranging from 12 % to 30 %. The mechanism underlying the development of severe illness caused by SFTS bunyavirus (SFTSV) is not yet fully understood. To evaluate the role of the TLR2 receptor pathway in regulating Treg function in the progression of SFTS disease and possible mechanisms, sequential serum samples from 29 patients with SFTS (15 mild, 14 severe cases) were examined. Flow cytometry was employed to scrutinize the phenotypic and functional characteristics of TLR2 expression on circulating CD4 T cells, CD8 T cells, and Tregs. In all admitted patients, the evaluation of correlations between the frequencies of the aforementioned cells and SFTS index (SFTSI) was conducted. For SFTS, the levels of TLR2 on CD4 T cells and Tregs were significantly heightened when compared to those in healthy subjects. Additionally, the expression of TLR2 on Tregs exhibited a positive correlation with Ki-67 expression in Tregs and the severity of disease. Additionally, compared with those in uninfected controls, the expression levels of NF-κB in Tregs were significantly increased. Collectively, Tregs may be activated and proliferate through the stimulation of the TLR2/NF-кB pathway in reaction to SFTSV infection.

RESUMEN

Senescence represents a major risk factor promoting liver fibrosis progression. Sirtuin 1 (SIRT1), an essential regulator of cellular senescence, may be involved in developing liver fibrosis. However, the role and mechanism of SIRT1 in liver fibrosis development were largely unknown. We constructed the liver fibrosis in aged rats induced by carbon tetrachloride (CCl4) and then transfected with GFP-SIRT1 adenoviral vectors. After that, we performed acetylomic analysis of liver tissue in aged rats to identify potential substrates of SIRT1. Furthermore, replicative senescent rat hepatocytes were pretreated with siRNA HnRNP U, SIRT1 adenoviral vectors, resveratrol, and siRNA SIRT1, following stimulation with H2O2. We found that the protein levels of SIRT1 and HnRNP U were down-regulation in aged rat liver fibrotic tissues, with an accumulation of NLRP3 inflammasome and activation of the p53/p21 pathway in liver tissue, as well as an increased level of plasma IL-1ß secretion. In comparison, these effects were reversed by overexpressing SIRT1 with adenoviral vectors. Acetylation of HnRNP U and its sites at K28 and K787 might be potential targets for SIRT1-mediated liver fibrosis in aged rats. Silencing HnRNP U reduced H2O2-induced up-regulation expression of p53, p21, and NLRP3 inflammasome at protein levels. Additionally, H2O2 induced high acetylation of HnRNP U in senescent hepatocytes, whereas overexpressing SIRT1 with adenoviral vectors and resveratrol deacetylate HnRNP U to inhibit NLRP3 inflammasome and the p53/p21 pathway. Besides, the silence of SIRT1 aggravated H2O2-induced p53-related senescence and NLRP3-related inflammation in senescent hepatocytes. Our findings suggested that deacetylation of HnRNPU mediated by SIRT1 attenuated liver fibrosis in the elderly by inhibiting p53/p21 pathway and NLRP3-related inflammation.

Asunto(s)

Senescencia Celular , Cirrosis Hepática , Proteína con Dominio Pirina 3 de la Familia NLR , Sirtuina 1 , Proteína p53 Supresora de Tumor , Animales , Sirtuina 1/metabolismo , Sirtuina 1/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Masculino , Ratas , Acetilación , Ratas Sprague-Dawley , Hepatocitos/metabolismo , Envejecimiento/metabolismo , Hígado/patología , Hígado/metabolismo , Inflamasomas/metabolismo , Tetracloruro de Carbono , Peróxido de Hidrógeno/metabolismo , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Resveratrol/farmacología , Resveratrol/uso terapéutico , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética

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BACKGROUND: Hepatitis B virus (HBV) infection is still a serious threat to global health and can lead to a variety of liver diseases, including acute and chronic hepatitis, liver cirrhosis, liver failure, hepatocellular carcinoma (HCC), and so on. At present, there are mainly two kinds of drugs for the treatment of hepatitis B at home and abroad: interferon (IFN) and nucleoside/nucleotide analogs (NAs). In recent years, natural compounds have been considered an important source for the development of new anti-HBV drugs due to their complex structure, diverse components, high efficiency, and low toxicity. Many studies have demonstrated that Solamargine has significant anticancer activity, but the antiviral effect is rarely studied. This study aimed to verify the anti-HBV effect of Solamargine and to explore the specific mechanism. METHOD: The relative expression of HBV pregenomic RNA (pgRNA) was detected by reverse transcription real-time fluorescence quantitative PCR (RT-qPCR). Northern blot and western blot were used to detect the relative expression of HBV pgRNA and target protein. PCR was used in the construction of HBV pg-promoter, ENII/BCP, and a series of gene deletion mutant fluorescent reporter vectors. The fluorescence relative expression of each mutant was detected by Renilla luciferase assay. RESULTS: By binding to MZF1 (Myeloid zinc finger protein 1, MZF1), Solamargine inhibits HBV core promoter activity, reduces pregenomic RNA level, and inhibits HBV, achieving antiviral effects.

Asunto(s)

Antivirales , Virus de la Hepatitis B , Regiones Promotoras Genéticas , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Humanos , Antivirales/farmacología , Células Hep G2 , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Replicación Viral/efectos de los fármacos , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología

RESUMEN

PURPOSE: To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. METHODS: A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. RESULTS: Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05). CONCLUSION: Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

Asunto(s)

Antibacterianos , Transferencia de Embrión , Endometritis , Resultado del Embarazo , Humanos , Femenino , Transferencia de Embrión/métodos , Endometritis/terapia , Embarazo , Adulto , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Resultado del Embarazo/epidemiología , Implantación del Embrión , Enfermedad Crónica , Histeroscopía/métodos , Índice de Embarazo , Criopreservación/métodos

RESUMEN

BACKGROUND: Patient adherence status to the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management strategy remains unclear, so are its influencing factors. We aim to investigate family members' adherence and its influencing factors during the family-based H. pylori infection management practice for related disease prevention. MATERIALS AND METHODS: Based on our previously family-based H. pylori survey in 2021, 282 families including 772 individuals were followed up 2 years after the initial survey to compare if the investigation and education might improve family member's adherence. The participant's adherence to H. pylori infection awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were followed up, and their influencing factors were also analyzed. RESULTS: The overall participant's adherence to recommendations on H. pylori awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were 77% (187/243), 67.3% (138/205), 60.1% (211/351), 46.5% (107/230), 45.6% (159/349), and 39.1% (213/545), respectively; and all showed improvements compared with their prior survey stages. The top reasons for rejection to treatment, retest, and gastroscopy were forgetting or unaware of H. pylori infection (30.3%), busy (32.8%), and asymptomatic (67.9%), respectively. Independent risk factor for low adherence to treatment was occupation (e.g., staff: OR 4.49, 95% CI 1.34-15.10). Independent favorable factors for treatment adherence were individuals at the ages of 18-44 years (OR 0.19, 95% CI 0.04-0.89) and had a large family size (e.g., four family members: OR 0.15, 95% CI 0.06-0.41); for retest adherence, it was individuals at the ages of 60-69 years (OR 0.23, 95% CI 0.06-0.97); for gastroscopy adherence, it was individuals at the age of 60-69 years (OR 0.46, 95% CI 0.28-0.75), and with gastrointestinal symptoms (OR 0.57, 95% CI 0.36-0.90). CONCLUSIONS: Family-based H. pylori management increases individual adherence to treatment, retest, and awareness, and there are also improved adherence to gastroscopy, publicity, and personal hygiene recommendations; further efforts are required to enhance the individual adherence rate for related disease prevention.

Asunto(s)

Familia , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , China/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Cooperación del Paciente/estadística & datos numéricos , Anciano , Encuestas y Cuestionarios , Control de Infecciones/métodos , Niño

RESUMEN

T cell exhaustion has emerged as a major hurdle that impedes the clinical translation of stimulator of interferon genes (STING) agonists. It is crucial to explore innovative strategies to rejuvenate exhausted T cells and potentiate the antitumor efficacy. Here, we propose an approach utilizing MSA-2 as a STING agonist, along with nanoparticle-mediated delivery of mRNA encoding interleukin-12 (IL-12) to restore the function of T cells. We developed a lipid nanoparticle (DMT7-IL12 LNP) that encapsulated IL12 mRNA. Our findings convincingly demonstrated that the combination of MSA-2 and DMT7-IL12 LNP can effectively reverse the exhausted T cell phenotype, as evidenced by the enhanced secretion of cytokines, such as tumor necrosis factor alpha, interferon gamma, and Granzyme B, coupled with reduced levels of inhibitory molecules such as T cell immunoglobulin and mucin domain-3 and programmed cell death protein-1 on CD8+ T cells. Furthermore, this approach led to improved survival and tumor regression without causing any systemic toxicity in melanoma and lung metastasis models. These findings suggest that mRNA encoding IL-12 in conjunction with STING agonists has the potential to confer superior clinical outcomes, representing a promising advancement in cancer immunotherapy.

Asunto(s)

Interleucina-12 , Ratones Endogámicos C57BL , ARN Mensajero , Interleucina-12/genética , Animales , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratones , Nanopartículas/química , Proteínas de la Membrana/agonistas , Proteínas de la Membrana/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Humanos , Femenino , Antineoplásicos/farmacología , Antineoplásicos/química , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Línea Celular Tumoral , Agotamiento de Células T

RESUMEN

BACKGROUND: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance. METHODS: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC. RESULTS: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC. CONCLUSIONS: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.

Asunto(s)

Metilación de ADN , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/sangre , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Método Doble Ciego , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Ácidos Nucleicos Libres de Células/sangre , Adulto

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Metal-assisted chemical etching (MacEtch) has emerged as a versatile technique for fabricating a variety of semiconductor nanostructures. Since early investigations in 2000, research in this field has provided a deeper understanding of the underlying mechanisms of catalytic etching processes and enabled high control over etching conditions for diverse applications. In this Review, we present an overview of recent developments in the application of MacEtch to nanomanufacturing and processing of III-V based semiconductor materials and other materials beyond Si. We highlight the key findings and developments in MacEtch as applied to GaAs, GaN, InP, GaP, InGaAs, AlGaAs, InGaN, InGaP, SiC, ß-Ga2O3, and Ge material systems. We further review a series of active and passive devices enabled by MacEtch, including light-emitting diodes (LEDs), field-effect transistors (FETs), optical gratings, sensors, capacitors, photodiodes, and solar cells. By reviewing demonstrated control of morphology, optimization of etch conditions, and catalyst-material combinations, we aim to distill the current understanding of beyond-Si MacEtch mechanisms and to provide a bank of reference recipes to stimulate progress in the field.

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Tumor vasculature is pivotal in regulating tumor perfusion, immune cell infiltration, metastasis, and invasion. The vascular status of the tumor is intricately linked to its immune landscape and response to immunotherapy. Vessel co-option means that tumor tissue adeptly exploits pre-existing blood vessels in the para-carcinoma region to foster its growth rather than inducing angiogenesis. It emerges as a significant mechanism contributing to anti-angiogenic therapy resistance. Different from angiogenic tumors, vessel co-option presents a distinctive vascular-immune niche characterized by varying states and distribution of immune cells, including T-cells, tumor-associated macrophages, neutrophils, and hepatic stellate cells. This unique composition contributes to an immunosuppressive tumor microenvironment that is crucial in modulating the response to cancer immunotherapy. In this review, we systematically reviewed the evidence and molecular mechanisms of vessel co-option in liver cancer, while also exploring its implications for anti-angiogenic drug resistance and the immune microenvironment, to provide new ideas and clues for screening patients with liver cancer who are effective in immunotherapy.

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Introduction: Medulloblastoma is the most common malignant brain tumor in children, often requiring intensive multimodal therapy, including chemotherapy with alkylating agents. However, therapy-related complications, such as therapy-related myeloid neoplasms (t-MNs), can arise, particularly in patients with genetic predisposition syndromes. This case report presents three pediatric cases of medulloblastoma with subsequent development of t-MNs, highlighting the potential role of genetic predisposition and the importance of surveillance for hematological abnormalities in long-term survivors. Case presentation: We describe three cases of pediatric medulloblastoma who developed t-MNs after receiving chemotherapy, including alkylating agents. Two of the patients had underlying genetic predisposition syndromes (TP53 pathologic variants). The latency period between initial diagnosis of medulloblastoma and the development of secondary cancer varied among the cases, ranging from 17 to 65 months. The three cases eventually succumbed from secondary malignancy, therapy-related complications and progression of primary disease, respectively. Conclusions: This report highlights the potential association between genetic predisposition syndromes and the development of therapy-related myeloid neoplasms in pediatric medulloblastoma survivors. It underscores the importance of surveillance for hematological abnormalities among such patients.

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Tenofovir disoproxil fumarate (TDF) seems to prevent hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV). However, the mechanism is still little known. This study aimed to investigate the the roles and mechanisms of TDF, tenofovir alafenamide fumarate (TAF), and entecavir (ETV) on the malignant characteristics of liver cancer cells. Using the wound-healing assays, transwell assays, matrigel transwell assays, and cell counting kit-8 (CCK-8) assays, it was possible to identify that TDF/TAF, inhibited migration, invasion, and proliferation of HepG2 cells and Huh7 cells. To investigate the mechanisms, we performed TOP/FOP-Flash system, Western blot, and RT-qPCR assays of liver cancer cells cultured with TDF/TAF and found a lower activity of Wnt/ß-catenin signaling pathway compared with control cells. Finally, Hepatitis C virus p7 trans-regulated protein 3 (p7TP3), a tumor suppressor in liver cancers, was significantly increased in HepG2 cells and Huh7 cells that treated with TDF/TAF. However, entecavir (ETV)-treated liver cancer cells showed no significant difference in the malignant characteristics of liver cancer cells, activity of Wnt/ß-catenin signaling pathway, and expression of p7TP3, compared with the control groups. To conclude, TDF/TAF maybe novel promising therapeutic strategy for liver cancers, including HCC and hepatoblastoma, via Wnt/ß-catenin signaling pathway, by up-regulating expression of the tumor suppressor, p7TP3.

Asunto(s)

Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Tenofovir/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Alanina/uso terapéutico , Adenina/uso terapéutico , Procesos Neoplásicos , Movimiento Celular , Antivirales/uso terapéutico

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Myricaria wardii Marquand 1929, endemic to the Tibet Plateau, is a perennial shrub with important medicinal and ecological values. In this study, the complete chloroplast (cp) genome of M. wardii was assembled, and the phylogenetic tree was reconstructed to evaluate the phylogenetic location of the species. The results showed that the cp genome size of the M. wardii was 155,299 bp, which contained a pair of inverted repeat (IR) regions (26,150 bp), a large single copy (LSC) region (84,715 bp), and a small single copy (SSC) region (18,284 bp). The total GC content of the cp genome was 36.30%. A total of 128 genes were annotated, consisting of 83 protein-coding genes, 37 tRNA genes and 8 rRNA genes. The phylogenetic analysis showed that M. wardii was closely related to M. prostrata. This study provides useful information for the conservation of this species and the phylogenetic analysis of Tamaricaceae.

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Severe acute respiratory syndrome (SARS)-coronavirus (CoV), Middle Eastern respiratory syndrome (MERS)-CoV, and SARS-CoV-2 have seriously threatened human life in the 21st century. Emerging and re-emerging ß-coronaviruses after the coronavirus disease 2019 (COVID-19) epidemic remain possible highly pathogenic agents that can endanger human health. Thus, pan-ß-coronavirus vaccine strategies to combat the upcoming dangers are urgently needed. In this study, four LNP-mRNA vaccines, named O, D, S, and M, targeting the spike protein of SARS-CoV-2 Omicron, Delta, SARS-CoV, and MERS-CoV, respectively, were synthesized and characterized for purity and integrity. All four LNP-mRNAs induced effective cellular and humoral immune responses against the corresponding spike protein antigens in mice. Furthermore, LNP-mRNA S and D induced neutralizing antibodies against SARS-CoV and SARS-CoV-2, which failed to cross-react with MERS-CoV. Subsequent evaluation of sequential and cocktail immunizations with LNP-mRNA O, D, S, and M effectively elicited broad immunity against SARS-CoV-2 variants, SARS-CoV, and MERS-CoV. A direct comparison of the sequential with cocktail regimens indicated that the cocktail vaccination strategy induced more potent neutralizing antibodies and T-cell responses against heterotypic viruses as well as broader antibody activity against pan-ß-coronaviruses. Overall, these results present a potential pan-ß-coronavirus vaccine strategy for improved preparedness prior to future coronavirus threats.

Asunto(s)

Liposomas , Nanopartículas , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Vacunas Virales , Animales , Ratones , Humanos , Vacunas de ARNm , SARS-CoV-2/genética , Vacunas contra la COVID-19 , Glicoproteína de la Espiga del Coronavirus/genética , Modelos Animales de Enfermedad , Vacunas Virales/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Anticuerpos Neutralizantes , ARN Mensajero/genética , Inmunidad , Anticuerpos Antivirales

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Compared with the traditional vaccine produced in embryonated chicken eggs, cell-based manufacturing represented by the Madin-Darby canine kidney (MDCK) cell line has a larger production scale and reduces the risk of egg shortage in a pandemic. Establishing a culture system that enables high production of the influenza virus is a key issue in influenza vaccine production. Here, a serum-free suspension culture of MDCK (sMDCK) cells was obtained from adherent MDCK (aMDCK) cells by direct adaptation. Viral infection experiments showed that viral yields of influenza A/B virus in sMDCK cells were higher than in aMDCK cells. Transcriptome analysis revealed that numerous interferon-stimulated genes (ISGs) exhibited reduced expression in sMDCK cells. To further clarify the mechanism of high viral production in sMDCK cells, we demonstrated the antiviral role of RIG-I and IFIT3 in MDCK cells by knockdown and overexpression experiments. Furthermore, suppression of the JAK/STAT pathway enhances the viral accumulation in aMDCK cells instead of sMDCK cells, suggesting the reduction in the JAK/STAT pathway and ISGs promotes viral replication in sMDCK cells. Taken together, we elucidate the relationship between the host innate immune response and the high viral productive property of sMDCK cells, which helps optimize cell production processes and supports the production of cell-based influenza vaccines.

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Saliva is an important exocrine fluid that is easy to collect and is a complex mixture of proteins and other molecules from multiple sources from which considerable biological information can be mined. Pig saliva, as an easily available biological liquid rich in bioactive ingredients, is rich in nucleic acid analytes, such as eggs, enzymes, amino acids, sugars, etc. The expression levels of these components in different diseases have received extensive attention, and the analysis of specific proteins, metabolites, and biological compositions in pig saliva has become a new direction for disease diagnosis and treatment. The study of the changes in analytes in pig saliva can provide a new strategy for early diagnosis, prognosis assessment, and treatment of diseases. In this paper, the detection methods and research progress of porcine salivary analytes are reviewed, the application and research progress of porcine salivary analytes in diseases are discussed, and the future application prospect is presented.

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Exploring two-dimensional (2D) room-temperature magnetic materials in the field of 2D spintronics remains a formidable challenge. The vast array of nonmagnetic 2D materials provides abundant resources for exploration, but the strategy to convert them into intrinsic room-temperature magnets remains elusive. To address this challenge, we present a general strategy based on surface halogenation for the transition from nonmagnetism to intrinsic room-temperature ferromagnetism in 2D MoS2 based on first-principles calculations. The derived 2D halogenated MoS2 are half-semimetals with a high Curie temperature (TC) of 430-589 K and excellent stability. In-depth mechanistic studies revealed that this marvelous nonmagnetism-to-ferromagnetism transition originates from the modulation of the splitting as well as the occupation of the Mo d orbitals by the synergy of lattice stretching and charge injection induced by the surface halogenation. This work establishes a promising route for exploring 2D room-temperature magnetic materials from the abundant pool of 2D nonmagnetic counterparts.